somewhat like the bacillus coli communis, but with a less
luxuriant growth. This organism, when taken from young
broth cultures twelve to twenty-four hours old—during the
period at which flagella are best seen—and examined microscopically,
exhibits very lively movements. When, as pointed
out by Gruber and Durham, blood-serum, in certain dilutions,
from a case of typhoid fever is added to such a culture, the broth,
at first turbid, owing to the suspended and moving microorganisms,
gradually becomes clear, and a deposit is formed
which is found to be made up of masses or clumps of typhoid
bacilli which have lost their motility. This reaction is so
characteristic and definite, that when the mixture is kept under
e.lamination under the microscope, it is quite possible to follow
the slowing-down movement and massing together of the
organisms. It is found, moreover, that normal diluted blood serum
has no such effect on the bacilli. This property of the
blood-serum is acquired at such an early date of the disease sometimes
even at the end of the first week—and occurs with such
regularity, that typhoid fever may now actually be diagnosed
by the presence or absence of this “agglutinating” property
in the blood. If serum taken from a patient supposed to be
suffering from typhoid fever, and diluted with saline solution
to 1 in 10, to 1 in 50, or in still greater dilution, causes the bacilli
to lose their motility and to become aggregated into clumps
within an hour, it may be concluded that the patient is suffering
from typhoid fever; if this agglutination be not obtained with
a dilution of 1 in 10, in from 15 to 30 minutes, experience has
shown that the patient is not suffering from this disease.
Certain other diseases, such as cholera, give a similar specific
serum reaction with their specific organisms. These sera have,
in addition, a slight common action—a general agglutinating
power—which, however, is not manifested except in concentrated
solutions, the higher dilutions failing to give any clumping
action at all, except with the specific bacillus associated with
the disease from which the patient, from whom the serum is
taken, is suffering.
Wright and Semple, working on Haffkine’s lines, introduced a method of vaccination against typhoid, corresponding somewhat to that devised by Haffkine to protect against cholera. They first obtained a typhoid bacillus of fairly constant virulence and of such strength and power of multiplication that an agar culture of 24 hours’ growth when divided into four, and injected hypodermically, will kill four fairly large guinea-pigs, each weighing 350 to 400 grammes. A similar culture emulsified in bouillon or saline solution and killed by heating for five minutes at 60° C. is a vaccine sufficient for from four to twenty doses. In place of the agar culture a bouillon culture heated for the same period may be used as the vaccine. In either case the vaccine is injected under the skin of the loin well above the crest of the ileum. This injection is usually followed by local tenderness and swelling within three or four hours, and swelling and tenderness in the position of the nearest lymphatic glands, marked malaise, headache, a general feeling of restlessness and discomfort and a rise of temperature. The blood of a patient so treated early causes agglutination of typhoid bacilli and acts on these bacilli much as does cholera serum in Pfeiffer’s reaction. At the end of ten days a second and stronger dose is given. After each injection there is, according to Wright, a “negative phase” during which the patient is somewhat more susceptible to the attacks of the typhoid bacillus. This negative phase soon passes off and a distinct positive or protected phase appears. The practical outcome of this is that wherever possible a patient who is going into a typhoid infected area should be vaccinated some little time before he sets out. There seems to be no doubt that if this be done a very marked, though not complete, protection is conferred. For a time the agglutinative and lytic powers of the serum continue to rise and the patient so vaccinated is far less susceptible to the action of the typhoid bacillus. It is recorded in favour of this method of treatment that of 4502 soldiers of the Indian army inoculated 0·98 % contracted typhoid, while of 25,851 soldiers of the same army who were not inoculated over 212% (2·54) contracted typhoid. Similarly, at Ladysmith, of the whole of the besieged soldiers only 1705 had been inoculated, but of these only 2% contracted typhoid, whilst of 10,529 uninoculated men 14% were attacked. Wright, who has been indefatigable in carrying out and watching this method of treatment, has been able to accumulate statistics dealing with 49,600 individuals—of these 8600 were inoculated, and 214% contracted typhoid, 12% of these succumbing to the disease. Of the 41,000 uninoculated men 534% contracted the disease, 21 % of those attacked succumbing.
Mediterranean or Malta Fever.—Until comparatively recently, Mediterranean fever was looked upon as a form of typhoid fever, which in certain respects it resembles; the temperature curve, however, has a more undulatory character, except in the malignant type, where the temperature remains high throughout the course of the attack. According to Hughes, this disease is widely distributed in the countries bordering upon the Mediterranean south of latitude 46° N., and along the Red Sea littoral. Analogous forms of fever giving a “specific” serum reaction with the micro coccus of this disease are also met with in parts of India, China, Africa and America.
The Micrococcus melitensis vel Brucei (1887), which is found most abundantly in the enlarged spleen of the patient suffering from Malta fever, is a very minute organism (0·33μ in diameter), ovoid or nearly round, arranged in pairs or in very short chains. If a drop of the blood taken directly from the spleen be smeared over the surface of agar nutrient medium, minute transparent colourless colonies appear; in thirty-six hours these have a slight amber tinge, and in four or five days from their first appearance they become opaque. These colonies, which flourish at the temperature of the human blood, cease to grow at the room-temperature except in summer, and if kept moist, soon die at anything below 60° F., though when dried they retain their vitality for some time. As the organism grows and multiplies in broth there is opacity of the medium at the end of five or six days, this being followed by precipitation, so that a comparatively clear supernatant fluid remains. It grows best on media slightly less alkaline than human blood; it is very vigorous and may resist desiccation for several weeks.
This organism is distinctly pathogenetic to monkeys, and its virulence may be so increased that other animals may be affected by it. Though unable to live in clean or virgin soil, it may lead a saprophytic existence in soil polluted with faecal matter. Hughes maintains that the “virus” leaves the body of goats and of man along with the faeces and urine. The importance of this in ambulatory cases is very evident, especially when it is remembered that goats feeding on grass, &c. which has come in contact with such urine are readily infected. It seldom appears to be carried for any considerable distance. Infection is not conveyed by the sputum, sweat, breath or scraping of the skin of patients, and infected dust does not seem to play a very important part in producing the disease. Hughes divides the fever into three types. In the malignant form the onset is sudden, there are headache, racking pain over the whole body, nausea and sometimes vomiting; the tongue is foul, coated and swollen, and the breath very offensive; the temperature may continue for some time at 103° to 105° F. The stools in the diarrhoea which is sometimes present may be most offensive. At the end of a few days the lungs become congested and pneumonia, the pulse weak, hyperpyrexia appears, and death ensues. A second type, by far the most common, is the “undulatory” type, in which there is remit tent pyrexia, separated by periods in which the patient appears to be improving. These pyrexial curves, from one to seven in number, average about ten days each, the first being the longest,—eighteen to twenty-three days. In an intermittent type, in which the temperature-curve closely resembles the hectic pyrexial curve of phthisis or suppuration, the "undulatory" character is also marked. A considerable number of toxic symptoms make their appearance—localized neuritis, synovitis, anaemia, emaciation, bronchial catarrh, weakness of the heart, neuralgia, profuse night-sweats and similar conditions. Patients otherwise healthy usually recover, even after prolonged attacks of the disease, but the mortality amongst patients suffering from organic mischief of any kind may be comparatively high. The diagnosis from malaria, phthisis, rheumatic affections and pneumonia may, in most cases, be made fairly easily, but the serum agglutinating reaction (first demonstrated by Wright in 1897) with cultures of the Micrococcus mcliiensis, corresponding to the typhoid reaction with the typhoid bacillus, is sometimes the only trustworthy feature by which a diagnosis may be made between this fever and the above-mentioned diseases. About 50% of the goats in Malta give a positive agglutinative reaction and about 10% excrete milk which contains the micro coccus.
Sir David Bruce, in his investigations on the tsetse fly disease, pointed out that certain wild animals although apparently in good health might serve as reservoirs for, or storehouses of, the N’gana parasite. He was therefore quite prepared to find
